The innate immune system is the first line of inducible defense against infectious disease. A key function of innate immunity is the detection of pathogen-associated molecular patterns (PAMPs) produced by infectious agents but not host cells and the launch of appropriate defense responses. Recent discoveries have revealed remarkable conservation in the recognition of PAMPs by leucine-rich-repeat (LRR) receptors and in signaling mechanisms of innate immune responses in plants, insects, worms, and mammals. We propose to use integrative molecular, cellular, biochemical, genomic, and genetic approaches to elucidate the signal transduction pathways induced by a well-defined bacterial flagellin peptide elicitor flg22 in the model plant Arabidopsis thaliana. The Research proposal will focus on the investigation of a MAPKKK (MEKK1) and a small GTPase (ROP11), that interact with the flg22 receptor kinase (FLS2) and mediate MAPK-dependent and MAPK-independent pathways, respectively, and converge on WRKY22/29 transcription factors in flg22 signaling. Protoplast transient assays and transgenic and mutant plants will be used for the studies. Four specific aims are: 1) Investigate the molecular mechanisms that link a specific MAPK cascade to the flg22 receptor FLS2 (a LRR receptor kinase) 2) Elucidate the function and mechanisms of ROP11-FLS2 interaction in flg22 signaling 3) Define the direct target genes of WRKY22/29 transcription factors in flg22 signaling 4) Determine the roles of the flg22 MAPK cascade, ROP11, and WRKY22/29 in plant defense responses against bacterial and fungal pathogens using transgenic and mutant plants. It has been well documented that flagellin peptide flg22 and many other pathogen-derived elicitors induce conserved signaling responses such as protein kinase activation, calcium influx, oxidative signaling, and transcriptional reprogramming. The proposed studies on the flg22 MAPK cascade, ROP11, and WRKY22/29 transcription factors that act downstream of FLS2 receptor kinase in early flg22 signaling will enhance our understanding of the molecular mechanisms underlying the early events of innate immune responses and improve our ability to manipulate durable disease resistance in plants.